Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis

灯盏花乙素治疗阿尔茨海默病的药理基础:抗氧化、抗凋亡

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作者:Xinyu Hu, Shanshan Teng, Jiawei He, Xiaoqi Sun, Mingzhao Du, Ling Kou, Xiaofeng Wang

Abstract

Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an L‑glutamic acid (L‑Glu)‑damaged HT22 cell apoptosis model and an aluminum chloride plus D‑galactose‑induced AD mouse model. In L‑Glu‑damaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase‑3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase‑3 activity assay kit, and propidium iodide and Annexin V staining. Furthermore, SC suppressed the accumulation of intracellular reactive oxygen species (ROS), restored the dissipation of mitochondrial membrane potential, enhanced the expression of antiapoptotic proteins and reduced the expression of pro‑apoptotic proteins, as determined by immunofluorescence assays and western blotting. In AD mice, SC enhanced vertical and horizontal movements in an autonomic activity test, and reduced the escape latency time in the water maze test. SC reduced the deposition of amyloid β1‑42 (Aβ1‑42) and the expression of phosphorylated‑Tau in the hippocampus as determined by immunohistochemistry analysis, but enhanced the serum levels of Aβ1‑42 of AD mice as determined by ELISA. ELISA analyses also revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of AD mice. The present study confirmed that the protective effects of SC in AD in vitro and in vivo are associated with its antioxidant and antiapoptotic properties.

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